56 research outputs found
Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
Cardiotoxicitat; Doxorubicina liposomal pegilada; SupervivĂšnciaCardiotoxicidad; Doxorubicina liposomal pegilada; SupervivenciaCardiotoxicity; Pegylated liposomal doxorubicin; SurvivalBackground: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).
Methods: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.
Results: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).
Conclusion: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.The rest of the study was supported by the collaborative group SOLTI
Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
Bevacizumab; Durvalumab; CĂ ncer de mama HER2 negatiuBevacizumab; Durvalumab; CĂĄncer de mama HER2 negativoBevacizumab; Durvalumab; HER2-negative breast cancerBackground
Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer.
Methods
Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10âmg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4âweeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as ânon-progressorsâ if they had clinical benefit (SD/PR/CR) at 4âmonths. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time.
Results
Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11âmonths; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4âmonths in triple-negatives; Pâ=â0.11). Clinical benefit rate at 2 and 4âmonths was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (Pâ=â0.73). Non-progressorsâ tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baselineâpost-bevacizumabâtumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors.
Conclusions
This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting.MQF is a recipient of the following grants: AES - PI16/00354 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF) and B2017/BMD3733 (Immunothercan-CM) - Call for Coordinated Research Groups from Madrid Region - Madrid Regional Government - ERDF funds. SM is a recipient of the following grants: Spanish Ministerio de EconomĂa y Competitividad (MINECO) (SAF2017-83732-R; AEI/FEDER, EU) and co-funded by Comunidad de Madrid (B2017/BMD3733; Immunothercan-CM). RC is a recipient RC is a recipient of the ISCIII grants PIE15/00068 and PI17/01865. The study was also funded by CRIS Contra el Cancer Foundation and Astra Zeneca Spain. Astra Zeneca Spain provided durvalumab
Clinical and histopathological risk associated with brain metastasis-free survival in breast cancer.
Novel biomarkers in primary breast core biopsies to predict poor response to neoadjuvant chemotherapy and appearance of metastases
Drug resistance has been one of the major
obstacles limiting the success of cancer chemotherapy.
In two thirds of breast cancer patients, large (>1cm)
residual tumors are present after neoadjuvant
chemotherapy (NCT). The residual tumor and involved
nodes have been indicators of relapse and survival very
important in breast cancer.
The goal of this preliminary study was to assess the
predictive significance of a panel of molecular
biomarkers, related with the response to treatment or
drug resistance to NCT, as determined on the diagnostic
tumor. The expression of 22 proteins was examined
using immunohistochemistry in tissue microarrays
(TMA) from 115 patients of stage II-III breast cancer,
treated with NCT. Among studied proteins, there are
some that are anti-apoptotic, pro-proliferative, cancer
stem cell markers and the Vitamin D Receptor. Other
proteins are involved in the identification of molecular
subtype, cell cycle regulation or DNA repair. Next, a
predictive signature of poor response was generated
from independent markers of predictive value. Tumors
that expressed four or five conditions (biomarkers of
chemoresistance with a determinated cutoff) were
associated with a 9-fold increase in the chances of these
patients of having a poor response to NCT. Additionally,
we also found a worse prognostic signature, generated
from independent markers of prognostic value. Tumors
which expressed two or three conditions of worst
prognostic, were associated with a 6-fold reduction in
Distant Disease Free Survival. In conclusion, finding
biomarkers of chemoresitance (ypTNM II-III) and
metastases can become a stepping stone for future
studies that will need to be assessed in a bigger scale
Patient preference for oral chemotherapy in the treatment of metastatic breast and lung cancer
[Objectives]: Although new therapies against metastatic cancer have been developed in recent decades, chemotherapy is still an important treatment option. Prolonged treatment and sideâeffects are often discouraging for patients, and in many cases, therapy is only palliative, not curative. This study explores patient preference for oral or intravenous (IV) chemotherapy in the treatment of metastatic breast or lung cancer.
[Methods]: It is a descriptive, open label, multicentre, nationâwide study, in which a 16âitem questionnaire consisting of singleâchoice questions scored on a 5âpoint Likert scale was administered to patients in a single visit, and another 11âitem questionnaire was selfâadministered by the patientâs oncologist.
[Results]: A total of 131 breast and lung cancer specialists at 64 hospitals enrolled 412 patients (lung cancer = 161; breast cancer = 251). To be eligible, patients must have already received IV therapy and at least 2 cycles of oral chemotherapy. Most (77%) patients expressed preference for oral therapy. Most considered their daily life was less disrupted with tablets (70.4%), had no trouble swallowing them (86.9%), and were not concerned about forgetting to take them (56.8%). Half (56.3%) were worried about problems related to drug infusion with IV therapy, 61.7% were concerned about nurses failing to find a suitable vein, and 63.1% were dissatisfied with hospital waiting times. A uniform response was obtained from both samples of patients.
[Conclusion]: Convenience, ease of administration, fewer side effects and better quality of life tilt the balance towards oral drug administration
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